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通过下一代测序研究利巴韦林治疗对克里米亚-刚果出血热病毒(CCHFV)基因突变的影响。

Investigating the effect of ribavirin treatment on genetic mutations in Crimean-Congo haemorrhagic fever virus (CCHFV) through next-generation sequencing.

作者信息

D'Addiego Jake, Elaldi Nazif, Wand Nadina, Osman Karen, Bagci Binnur Koksal, Kennedy Emma, Pektas Ayse Nur, Hart Eilish, Slack Gillian, Hewson Roger

机构信息

UK Health Security Agency, Salisbury, UK.

Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.

出版信息

J Med Virol. 2023 Feb;95(2):e28548. doi: 10.1002/jmv.28548.

Abstract

Crimean-Congo haemorrhagic fever (CCHF) is the most widespread tick-borne viral haemorrhagic fever affecting humans, and yet a licensed drug against the virus (CCHFV) is still not available. While several studies have suggested the efficacy of ribavirin against CCHFV, current literature remains inconclusive. In this study, we have utilised next-generation sequencing to investigate the mutagenic effect of ribavirin on the CCHFV genome during clinical disease. Samples collected from CCHF patients receiving ribavirin treatment or supportive care only at Sivas Cumhuriyet University Hospital, Turkey, were analysed. By comparing the frequency of mutations in each group, we found little evidence of an overall mutagenic effect. This suggests that ribavirin, administered at the acute stages of CCHFV infection (at the World Health Organization-recommended dose) is unable to induce lethal mutagenesis that would cause an extinction event in the CCHFV population and reduce viremia.

摘要

克里米亚-刚果出血热(CCHF)是影响人类的最广泛的蜱传病毒性出血热,但目前仍没有针对该病毒(CCHFV)的许可药物。虽然多项研究表明利巴韦林对CCHFV有效,但目前的文献仍无定论。在本研究中,我们利用下一代测序技术来研究利巴韦林在临床疾病期间对CCHFV基因组的诱变作用。对仅在土耳其锡瓦斯 Cumhuriyet 大学医院接受利巴韦林治疗或支持性护理的CCHF患者采集的样本进行了分析。通过比较每组中的突变频率,我们几乎没有发现整体诱变作用的证据。这表明,在CCHFV感染急性期(按照世界卫生组织推荐剂量)给予利巴韦林,无法诱导导致CCHFV群体灭绝事件并降低病毒血症的致死性诱变。

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